Erlotinib in combination with pemetrexed/cisplatin for leptomeningeal metastases and cerebrospinal fluid drug concentrations in lung adenocarcinoma patients after gefitinib faliure

Target Oncol. 2015 Mar;10(1):135-40. doi: 10.1007/s11523-014-0326-9. Epub 2014 Jul 2.


Limited treatment options are available for lung cancer with brain metastases. Recent reports indicated that erlotinib and pemetrexed had synergistic effects in lung adenocarcinoma. Thus, we speculated that erlotinib plus pemetrexed/cisplatin may be more effective for the treatment of refractory central nervous system metastases in patients after gefitinib failure. Six lung adenocarcinoma patients with leptomeningeal metastasis (LM) who showed initial good response to gefitinib and subsequent gefitinib resistance were enrolled in this retrospective study. Five of the six patients had an epidermal growth factor receptor (EGFR) mutation in the primary tumor tissues or plasma. One patient showed complete remission, two patients showed a partial response, and two patients had stable disease. Performance and symptoms improved in the six patients. The survival time after the combination therapy was from 8 to 15 months (median, 9 months). There was no significant difference in cerebrospinal fluid (CSF) penetration rates of erlotinib between the erlotinib-only and the combination groups (P = 0.44). Erlotinib combined with pemetrexed/cisplatin may be effective in the treatment of LM in EGFR mutation patients after gefitinib failure. Small but measurable penetration of erlotinib and pemetrexed into the CSF was observed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chromatography, Liquid
  • Cisplatin / administration & dosage
  • Cisplatin / cerebrospinal fluid
  • Drug Resistance, Neoplasm / drug effects*
  • Erlotinib Hydrochloride / administration & dosage
  • Erlotinib Hydrochloride / cerebrospinal fluid
  • Female
  • Gefitinib
  • Genes, erbB-1
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Meningeal Carcinomatosis / drug therapy*
  • Meningeal Carcinomatosis / secondary
  • Middle Aged
  • Mutation
  • Pemetrexed / administration & dosage
  • Pemetrexed / cerebrospinal fluid
  • Quinazolines / therapeutic use
  • Retrospective Studies
  • Tandem Mass Spectrometry


  • Quinazolines
  • Pemetrexed
  • Erlotinib Hydrochloride
  • Cisplatin
  • Gefitinib